R01DA16065 is focused on hepatitis C virus (HCV) infection in HIV-infected injection drug users (IDUs). Among HIV-infected IDUs, HCV disease is a leading cause of morbidity and mortality. Despite the medical urgency, fundamental questions about HCV disease and its management have not been conclusively answered. The true prevalence of significant liver disease is unknown, since estimates have been derived from HIV-infected persons who underwent liver biopsy following referral for HCV treatment. Further, due to limited applicability of liver biopsy, few data exist regarding the relationship of HCV disease stage and clinically important outcomes such as end-stage liver disease (ESLD). While CD4 cell and HIV RNA quantification are powerful non-invasive measures used to stratify HIV disease risk and define the need for treatment, such non-invasive, prognostic markers have not been established for HCV disease. Finally, the management of HCV disease in HIV-infected IDUs is challenging; our research has shown that net HCV treatment effectiveness is low in HIV-infected persons. Until recently, a major limitation to HCV disease research in coinfected IDUs has been the measurement of disease stage. Transient elastography is a novel, non-invasive method based on the observation that liver elasticity decreases as liver fibrosis increases. Rapid liver stiffness measurements can be obtained in the clinic to determine HCV disease stage. Our research has shown that HCV disease in coinfected IDUs can be accurately and safely measured by assessment of liver stiffness. In our first aim, we will apply this novel method to determine the population prevalence of HCV disease in coinfected IDUs independent of referral for HCV treatment, providing one of the first valid estimates of the true HCV disease burden. In our second aim, we will ask whether the marked differences in HCV disease outcomes (e.g., ESLD) can be explained by liver stiffness as assessed by elastography; we'll test the hypothesis that increased liver stiffness is associated with greater risk of incident ESLD. Our third aim will test the hypothesis that a highly innovative behavioral reinforcement (contingent voucher incentives) will improve the effectiveness of current and future HCV treatments in coinfected IDUs. HCV disease remains a significant unmet challenge in HIV-infected persons. Answers to these fundamental questions are needed to advance this field and will provide much needed data to influence the development of policies and guidelines for the management of HCV disease, a leading cause of death in HIV-infected IDUs. PUBLIC HEALTH RELEVANCE: The application is focused on hepatitis C virus (HCV) infection in HIV-infected injection drug users (IDUs). Among HIV-infected IDUs, HCV disease is a leading cause of morbidity and mortality. This research applies two highly innovative interventions, transient elastography and contingent behavioral reinforcement, to the evaluation and management of persons with HIV/HCV coinfection.